NUS researchers are honing in on a drug that could be used to treat severe dengue, thanks to a recent study which discovered that asthma attacks and a symptom of the dengue disease have something in common. They are conducting a clinical trial from 2015 to 2016 to determine the effectiveness of Ketotifen, which has been used as an asthma and allergy medicine for 30 years, to treat symptoms of the viral infection.
The trial, led by NUS Yong Loo Lin School of Medicine's Professor Paul Tambyah, is being conducted at the Investigational Medical Unit at NUS with dengue patients from the National University Hospital (NUH) and Singapore General Hospital (SGH). The research that preceded the trial was conducted at the Duke-NUS Graduate Medical School Singapore's (Duke-NUS) Emerging Infectious Diseases Programme by Assistant Professor Ashley St John and her team.
People suffering from asthma and allergy attacks as well as dengue fever are susceptible to vascular leakage, where fluids escape from blood vessels into other parts of the body. The KETODEN trial tests the hypothesis that Ketotifen, which alleviates vascular leakage in those suffering from asthma and allergies, can also treat the same complication in those infected with dengue.
Vascular leakage is caused by the activation of a type of immune cell called the mast cell. Ketotifen works by blocking the activation of mast cells, which helps stop the leakage. The loss of fluid from blood vessels reduces a person's overall blood volume and creates problems due to excessive fluid build-up in the lungs or abdomen. Excessive or uncontrolled vascular leakage leads to dengue haemorrhagic fever or dengue with complications in patients.
Currently, dengue patients are often managed in outpatient clinics by providing fever and pain relief, and advice on fluid intake. If vascular leakage is detected, or if patients have other complications, then they may be admitted for observation or given intravenous fluids to prevent shock. However, there is no approved treatment to prevent vascular leakage during dengue infection.
Last year, Singapore saw a rise in the number of dengue cases to almost 900 a week in peak months. Almost 3,000 cases of dengue fever have been reported this year.